Dataset Information

None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis.

ABSTRACT:

Background & aims

A combination of pegylated interferon-alpha and ribavirin (PR) is the standard therapy for patients with chronic hepatitis C. The impact of polymorphism of interleukin-28B (IL28B) on sustained virological response (SVR) to PR has been well documented in patients with CHC genotype-1 (GT1), but it is controversial in genotype-2 (GT2) CHC patients. This study investigated the predictability of six single nucleotide polymorphisms (SNP) of IL28B on the treatment responses of PR in patients with CHC GT2.

Method

197 CHC GT2 consecutive patients who received PR treatment in our prospective cohort were enrolled. Hepatitis C virus (HCV) genotyping, quantification of HCV-RNA and genotyping of the ten SNPs of IL28B were performed. Six SNPs of IL28B were chosen for analysis. The propensity score matching (PSM) analysis was applied using patients with CHC GT1 in another prospective cohort as a positive comparison to avoid covariate bias.

Results

The distribution of the six SNPs was similar in GT1 and GT2 patients. Five of these SNPs had strong association with treatment responses in GT1 but not in GT2 patients. After PSM analysis, these five SNPs still showed strong association with rapid virological response (RVR), cEVR and SVR in GT1 and had no influence in GT2 patients. Furthermore, rs12979860 and baseline viral load were the predictors for both RVR and SVR in GT1 patients. However, only baseline viral load could predict RVR and SVR in GT2 patients. In addition, in patients without RVR, rs12979860 was the only predictor for SVR in GT1 but no predictor for SVR was found in GT2.

Conclusions

The genetic polymorphisms of IL28B had no impact on treatment responses in GT2 patients.

SUBMITTER: Jeng WJ

PROVIDER: S-EPMC3500244 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis.

Jeng Wen-Juei WJ Lin Chun-Yen CY Chen Ji-Yih JY Huang Chang-Wen CW Huang Chien-Hao CH Sheen I-Shyan IS

PloS one 20121116 11

<h4>Background & aims</h4>A combination of pegylated interferon-alpha and ribavirin (PR) is the standard therapy for patients with chronic hepatitis C. The impact of polymorphism of interleukin-28B (IL28B) on sustained virological response (SVR) to PR has been well documented in patients with CHC genotype-1 (GT1), but it is controversial in genotype-2 (GT2) CHC patients. This study investigated the predictability of six single nucleotide polymorphisms (SNP) of IL28B on the treatment responses of ...[more]

PMID: 23173032

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Project description:PurposeThe purpose of this study was to evaluate the effectiveness of either hydroxychloroquine, triple combination therapy (TCT), favipiravir, dexamethasone, remdesivir, or COVID-19 convalescent plasma (CCP) in comparison with standard-of-care for hospitalized patients with COVID-19 using real-world data from Saudi Arabia.Patients and methodsA secondary database analysis was conducted using the Saudi Ministry of Health database for patients with COVID-19. Adult (≥18 years) hospitalized patients with COVID-19 between March 2020 and January 2021 were included in the analysis. A propensity score matching technique was used to establish comparable groups for each therapeutic approach. Lastly, an independent t-test and chi-square test were used to compare the matching groups in the aspects of the duration of hospitalization, length of stay (LOS) in intensive care units (ICU), in-hospital mortality, and composite poor outcome. Multilevel logistic regression model was used to assess the association between the severity stage of COVID-19 and the outcomes while using the medication or intervention used as a grouping variable in the model.ResultsThe mean duration of hospitalization was significantly longer for patients who received TCT, favipiravir, dexamethasone, or CCP compared to patients who did not receive these therapies, with a mean difference ranging between 2.2 and 4.9 days for dexamethasone and CCP, respectively. Furthermore, the use of favipiravir or CCP was associated with a longer stay in ICU. Remdesivir was the only agent associated with in-hospital mortality benefit. A higher risk of mortality and poorer composite outcome were associated with the use of favipiravir or dexamethasone. However, the logistic regression model reveled that the difference between the two matched cohorts was due to the severity stage not the medication. Additionally, the use of hydroxychloroquine, TCT, or CCP had no impact on the incidence of in-hospital mortality or composite poor outcomes.ConclusionRemdesivir was the only agent associated with in-hospital mortality benefit. The observed worsened treatment outcomes associated with the use of dexamethasone or FPV shall be attributed to the severity stage rather than the medication use. In light of these varied results, additional studies are needed to continue evaluating the actual benefits of these therapies.

Project description:BackgroundThe diagnostic process is a key element of medicine but it is complex and prone to errors. Infectious diseases are one of the three categories of diseases in which diagnostic errors can be most harmful to patients. In this study we aimed to estimate the effect of initial misdiagnosis of the source of infection in patients with bacteraemia on 14 day mortality using propensity score methods to adjust for confounding.MethodsData from a previously described longitudinal cohort of patients diagnosed with monobacterial bloodstream infection (BSI) at the Leiden University Medical Centre (LUMC) between 2013 and 2015 were used. Propensity score matching and inversed probability of treatment weighting (IPTW) were applied to correct for confounding. The average treatment effect on the treated (ATT), which in this study was the average effect of initial misdiagnosis on the misdiagnosed (AEMM), was estimated. Methodological issues that were encountered when applying propensity score methods were addressed by performing additional sensitivity analyses. Sensitivity analyses consisted of varying caliper in propensity score matching and using different truncated weights in inversed probability of treatment weighting.ResultsData of 887 patients were included in the study. Propensity scores ranged between 0.015 and 0.999 and 80 patients (9.9%) had a propensity score > 0.95. In the matched analyses, 35 of the 171 misdiagnosed patients died within 14 days (20.5%), versus 10 of the 171 correctly diagnosed patients (5.8%), yielding a difference of 14.6% (7.6%; 21.6%). In the total group of patients, the observed percentage of patients with an incorrect initial diagnosis that died within 14 days was 19.8% while propensity score reweighting estimated that their probability of dying would have been 6.5%, if they had been correctly diagnosed (difference 13.3% (95% CI 6.9%;19.6%)). After adjustment for all variables that showed disbalance in the propensity score a difference of 13.7% (7.4%; 19.9%) was estimated. Sensitivity analyses yielded similar results. However, performing weighted analyses without truncation yielded unstable results.ConclusionThus, we observed a substantial increase of 14 day mortality in initially misdiagnosed patients. Furthermore, several patients received propensity scores extremely close to one and were almost sure to be initially misdiagnosed.

Dataset Information

None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis.

Background & aims

Method

Results

Conclusions

Publications

None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis.

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